1. Field of the Invention
This invention is directed to mammalian primate erythrocytes to which have been bound cross-linked monoclonal antibodies (heteropolymers) specific for both the erythrocyte complement receptor protein (CR1), and (a 2nd antibody bound thereto specific for) a circulating antigen. Methods of using these "franked" erythrocytes in diagnostic or assay methodology and therapeutic applications are also addressed.
2. Background of the Prior Art
Mammalian primate erythrocytes (RBC's) have been identified as essential to the body's ability to clear antibody/antigen immune complexes from the blood. Specifically, the RBC receptor (CR1), known to be specific for certain activated complement proteins (C3b, C3bi and C4b), has been implicated as playing an important role in the primate's defense against microorganism infection by facilitating the neutralization and clearance of certain pathogenic substances. Other evidence shows that the binding of these immune complexes to RBC's at the CR1 site provides a vehicle for rapid clearance of potentially pathogenic immune complexes from circulation. Enhancement of phagocytosis and circulatory transport of immune complexes have both been advanced as mechanisms by which the RBC's function in this immune response. See, e.g., Nelson, Science 118, 733-737 (1953) and Hebert et al, Kidney Int., 31, 877-885 (1987). In any event, defects in aspects of this RBC clearance method have been demonstrated to be at least statistically related to a number of diseases and are believed to presage various disease activities.
Notwithstanding the importance of this function of the RBC and the immune system, it is apparent that the RBC binding and clearance capacity therefore is confined to immune complexes recognized by the CR1 receptor, that is the the immune complexes must contain large amounts of at least one of the activated Complement proteins C3b, C3bi, or C4b. Thus, the mammalian primate or human body has no normal capacity to take advantage of the clearance system provided by the RBC binding ability to remove antigens not complexed with the identified activated complement proteins. It remains an object of those of skill in the art to augment the natural capacity of the mammalian circulatory system to clear antigens through RBC binding ability to include the ability to bind immune complexes (antigen/antibody complexes) via CR1 to RBC's in the absence of activated complement proteins. These augmented RBC's would be useful both in a therapeutic sense, as well as in an assay mode to identify the presence or absence of specific antigens.